Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection.
Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.
Russo
Rossella
R
Department of Pharmacobiology, University of Calabria, 87036 Arcavacata di Rende, Italy.
Cavaliere
Federica
F
Rombolà
Laura
L
Gliozzi
Micaela
M
Cerulli
Angelica
A
Nucci
Carlo
C
Fazzi
Elisa
E
Bagetta
Giacinto
G
Corasaniti
Maria Tiziana
MT
Morrone
Luigi Antonio
LA
D000818:Animals; D002154:Calpain / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D018696:Neuroprotective Agents; D014451:Ubiquinone; D018698:Glutamic Acid; D002154:Calpain; C024989:coenzyme Q10